Tablets & Capsules

camfilapc.com US Pharmacopeia 14 Surrogate material To choose a surrogate material that is sufficiently similar to your API, con- sider characteristics such as particle size, flowability, electrostatic proper- ties, and sensitivity to moisture, heat, and light. Detection-limit sensitivity will vary by surrogate material. If you are handling an API that is very haz- ardous, the surrogate's detection-limit sensitivity should be extremely low— down to micrograms or picograms— to ensure that the system is perform- ing properly. Certain surrogate materials are inert, with no handling or decontamination issues, while other materials have an active component. Conducting the test at your facility might not be ap- propriate in the second case, so you will have to test at a contracted facility. Particle size distribution is important. For example, lactose is a common sur- rogate material because it's inert, and its detection-limit sensitivity levels are low: 0.01 μg/m 3 for an eight-hour total weight average (TWA) and 0.17 μg/m 3 for 15 minutes. With lactose, the test operators don't need personal protec- tive equipment (PPE) unless they are lactose intolerant. The detection sensitivity of naproxen sodium is extremely low, with a sensi- tivity of 0.0005 μg/m 3 for an eight-hour TWA and 0.017 μg/m 3 for 15 minutes. This sensitivity makes it a great surro- gate material, especially for testing an extremely hazardous material, but it's an active material. If you're testing in your facility, you need to be concerned with decontamination, cross contami- nation, and exposure, and the testers might need to use PPE. Target performance level If an API doesn't have an official expo- sure limit, you will have to identify one using a contract lab and your testing team. For example, you may determine that a process-control target of 30 per- cent of the exposure limit for the sur- rogate indicates a robust containment system. It's also important to validate the analytical methods for the test sample, preferably using an accredited laboratory. Key components of a vali- dation protocol should include: • Selectivity. Detection without significant interferences; • Linearity. A linear response over the working range; • Recovery and precision. Sufficient detection sensitivity to enable the measurement method to meet stringent requirements; • Sample stability. Data for all conditions, including transportation and storage; and • Robustness. Detection unaffected by small changes in analytical conditions. Testing activities You must develop the surrogate test- ing protocol prior to testing with the help of your health and safety depart- ment, a certified consultant, and/or the International Society for Pharmaceuti- cal Engineering (ISPE) Good Practice Guide [1]. Include test methodologies such as information recording, sample recovery, data logging, and analysis. You also must determine the level of operator training required. Using a dust collection expert to conduct the testing manipulations versus some- one who isn't familiar with the system will yield different results. Usually, trained dust collector operators con- duct tests to demonstrate a system's maximum performance, but if you The testing team can grade each dust-containment manipulation, such as a bag-in/bag-out process.

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